The Molluscum Contagiosum Virus protein MC163 localizes to the mitochondria and dampens mitochondrial mediated apoptotic responses

Coutu, Jesse; Ryerson, Melissa R.; Bugert, Joachim Jakob; Nichols, Daniel Brian

doi:10.1016/j.virol.2017.02.017

Cited by 13 publications

(11 citation statements)

References 54 publications

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“…Like the SFV proteins, the MC163 protein is predicted to be inactive as it lacks amino acids critical for SOD enzymatic activity. We recently reported that MC163 contains a mitochondrial localization sequence in the N-terminal region [ 213 ]. As predicted, MC163 co-localized with pMTurquoise2-mito, a cyan fluorescent protein engineered with a mitochondrial localization sequence (MLS) sequence [ 213 ].…”

Section: Poxvirus Inhibitors Of the Intrinsic Pathwaymentioning

confidence: 99%

“…We recently reported that MC163 contains a mitochondrial localization sequence in the N-terminal region [ 213 ]. As predicted, MC163 co-localized with pMTurquoise2-mito, a cyan fluorescent protein engineered with a mitochondrial localization sequence (MLS) sequence [ 213 ]. Using truncated MC163 mutant proteins, we confirmed that the N-terminal region of MC163 was required for its mitochondria localization.…”

Section: Poxvirus Inhibitors Of the Intrinsic Pathwaymentioning

confidence: 99%

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Poxviruses Utilize Multiple Strategies to Inhibit Apoptosis

Nichols

Martini

Cottrell³

2017

Viruses

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Cells have multiple means to induce apoptosis in response to viral infection. Poxviruses must prevent activation of cellular apoptosis to ensure successful replication. These viruses devote a substantial portion of their genome to immune evasion. Many of these immune evasion products expressed during infection antagonize cellular apoptotic pathways. Poxvirus products target multiple points in both the extrinsic and intrinsic apoptotic pathways, thereby mitigating apoptosis during infection. Interestingly, recent evidence indicates that poxviruses also hijack cellular means of eliminating apoptotic bodies as a means to spread cell to cell through a process called apoptotic mimicry. Poxviruses are the causative agent of many human and veterinary diseases. Further, there is substantial interest in developing these viruses as vectors for a variety of uses including vaccine delivery and as oncolytic viruses to treat certain human cancers. Therefore, an understanding of the molecular mechanisms through which poxviruses regulate the cellular apoptotic pathways remains a top research priority. In this review, we consider anti-apoptotic strategies of poxviruses focusing on three relevant poxvirus genera: Orthopoxvirus, Molluscipoxvirus, and Leporipoxvirus. All three genera express multiple products to inhibit both extrinsic and intrinsic apoptotic pathways with many of these products required for virulence.

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Section: Poxvirus Inhibitors Of the Intrinsic Pathwaymentioning

confidence: 99%

Section: Poxvirus Inhibitors Of the Intrinsic Pathwaymentioning

confidence: 99%

Poxviruses Utilize Multiple Strategies to Inhibit Apoptosis

Nichols

Martini

Cottrell³

2017

Viruses

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“…The superoxide anion has been shown to be antipoptotic and to induce cell proliferation [14]. Molluscum contagiousum has been shown to encode a SOD-like protein, which has been shown to bind the mitochondrial apoptotic factors Bak/Bax thereby dampening the apoptotic response [15].…”

Section: Introductionmentioning

confidence: 99%

“…The Molluscum Contagiosum MC163 protein has been shown to possess properties of a Cu,Zn SOD [15] and is hypothesized to prevent formation of the Bak/Bax complex in the mitochondrion. Although Cu,Zn SOD is a cytosolic protein, it has also been shown to localize to the mitochondrion [22,23].…”

Section: Introductionmentioning

confidence: 99%

Influence of the lumpy skin disease virus (LSDV) superoxide dismutase homologue on host transcriptional activity, apoptosis and histopathology

Munyanduki

Douglass

Offerman

et al. 2020

Journal of General Virology

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Lumpy skin disease virus (LSDV), a Capripoxvirus, is of economic importance in the cattle industry and is controlled by vaccination. A comparison was made of the host response to the two LSDV vaccines Neethling and Herbivac LS, with reference to the well-studied Orthopoxvirus, modified vaccinia Ankara (MVA), in a mouse model. Because the vaccines differ at the superoxide dismutase homologue (SOD) gene locus, recombinant SOD knock-out and knock-in nLSDV vaccines were constructed and all four vaccines were tested for the induction and inhibition of apoptosis. The SOD homologue was associated both with induction of apoptosis as well as inhibition of camptothecin-induced apoptosis. Histological analysis of chorioallantoic membranes of fertilized hens’ eggs infected with the four different vaccines indicated marked mesodermal proliferation associated with vaccines containing the full-length SOD homologue as well as increased immune cell infiltration. Our findings suggest that the SOD homologue may influence vaccine immunogenicity.

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“…Therefore, we need to explore whether RLS produced cytotoxic effect by triggering mitochondrial dysfunctions. Mitochondrial dysfunctions can be indicated by the depolarization of MMP and it is one of the early events that trigger apoptosis . The JC‐1 was used as a fluorescence probe to investigate the alteration of MMP in MG‐63 cells.…”

Section: Resultsmentioning

confidence: 99%

3D Printed Composite Scaffolds Incorporating Ruthenium Complex–Loaded Liposomes as a Delivery System to Prevent the Proliferation of MG‐63 Cells

Yang

Wang

Liao

et al. 2019

Macro Materials & Eng

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Owing to the propensity of osteosarcoma to recur and metastasize, the administration of a topical treatment to enhance the therapeutic effect of conventional therapy is necessary. To develop a locally released drug delivery system (DDS) to inhibit the growth and recurrence of osteosarcoma, hydrophobically modified silica nanoparticles (m‐SiO2)/poly(ε‐caprolactone) (PCL) porous scaffolds are fabricated by 3D printing emulsion inks. Ruthenium‐loaded PEGylated liposomes (RL) are then incorporated into the scaffolds to obtain the Ruthenium‐loaded PEGylated liposome scaffold (RLS) composite. The emulsion inks and the density, porosity, morphology, and mechanical properties of the scaffolds are characterized. The results indicate that the composite DDS has a relatively uniform porous structure with good mechanical properties. Drug is released from RLS in a relatively sustained manner over 48 h, which demonstrates the potential of RLS as a drug carrier. In addition, the MG‐63 cell viability and apoptosis rate are evaluated by MTT assays. The cell experiments reveal that RLS triggers mitochondrial dysfunction resulting in MG‐63 cell apoptosis. All the results indicate that RLS provides a promising approach for improving the treatment of osteosarcoma.

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The Molluscum Contagiosum Virus protein MC163 localizes to the mitochondria and dampens mitochondrial mediated apoptotic responses

Cited by 13 publications

References 54 publications

Poxviruses Utilize Multiple Strategies to Inhibit Apoptosis

Poxviruses Utilize Multiple Strategies to Inhibit Apoptosis

Influence of the lumpy skin disease virus (LSDV) superoxide dismutase homologue on host transcriptional activity, apoptosis and histopathology

3D Printed Composite Scaffolds Incorporating Ruthenium Complex–Loaded Liposomes as a Delivery System to Prevent the Proliferation of MG‐63 Cells

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